European Respiratory Journal最新文献

Background: Biologics can induce remission in some patients with severe asthma, however, little is known about pre-biologic disease trajectories and their association with outcomes from biological treatment. We aimed to identify long-term trajectories of disease progression in patients initiating biologics and investigate trajectory associations with disease burden and impact on biologic therapy efficacy.

Methods: Patients in the Danish Severe Asthma Registry initiating biologic therapy between 2016-2022 were included and followed retrospectively in prescription databases starting 1995. We performed sequence analysis for inhaled corticosteroid (ICS) treatment intensity over time combined with unsupervised trajectory clustering.

Results: In total, 755 patients were included and three pre-biologic disease trajectories were identified: Chronic severe asthma (26%), Gradual onset severe asthma (35%), Recent, sudden onset severe asthma (39%). Chronic severe asthma patients were older, had the longest disease duration (35 years), the most impaired pulmonary function, the highest comorbidity prevalence and the lowest employment rate. Recent, sudden onset severe asthma patients were younger, had shorter disease duration (5 years), more tobacco exposure and the least impaired lung function. Gradual onset severe asthma had an intermediate burden of disease. The Chronic severe asthma cluster demonstrated the lowest prevalence of remission (17%) compared to the Gradual onset severe asthma (29%) and Recent onset severe asthma (32%) clusters.

Conclusions: Three pre-biologic disease trajectories were identified, with increased disease duration and activity associating with asthma- and comorbidity burden. Early intervention may be key to prevent irreversible adverse outcomes for patients with severe asthma.

Rationale: Although a relationship between the Gas6/AXL pathway and pulmonary fibrosis (PF) has been suggested, the precise mechanisms and clinical implications of the AXL pathway in idiopathic pulmonary fibrosis (IPF) are still unclear.

Methods: Constitutive and conditional AXL-knockout mice were generated and injected with bleomycin (BLM) to induce pulmonary fibrosis. The expression of AXL and macrophage subtypes in BLM-injected mice and patients with IPF was analysed using flow cytometry. The therapeutic effects of the AXL inhibitors were examined.

Results: AXL-deficient mice were resistant to BLM-induced pulmonary fibrosis and had a lower degree of M2-like macrophage differentiation than wild-type mice. Interestingly, AXL expression in monocytes was enhanced according to the progression of BLM-induced pulmonary fibrosis (PF), and these results were especially prominent in Ly6C^high monocytes. Gene silencing or inhibitor treatment with AXL inhibited the differentiation of M2-like macrophages during bone marrow-derived macrophage (BMDMs) differentiation. These results were confirmed through experiments using AXL^fl/flLysMCre+ mice and systems with depletion and reconstitution of macrophages. In line with these results, patients with severe IPF had higher AXL expression in monocytes, high GAS6 levels, and an enhanced population of M2-like macrophages than those with mild IPF. Lastly, treatment with AXL inhibitors ameliorated BLM-induced PF and improved survival rate.

Conclusions: The AXL pathway in classical monocytes contributed to PF progression through the induction of M2-like macrophage differentiation. Therefore, targeting AXL may be a promising therapeutic option for PF.

Background: This multicentre, international, retrospective study aimed to investigate whether respiratory system reactance (X _rs) assessed by respiratory oscillometry on day 7 of life is associated with respiratory outcomes in preterm infants below 32 weeks gestational age (GA).

Methods: Sinusoidal pressure oscillations (2-5 cmH₂O peak-to-peak, 10 Hz) were superimposed on the positive end-expiratory pressure. We assessed the association of X _rs z-score with the duration of respiratory support using linear regression and with bronchopulmonary dysplasia (BPD) using logistic regression. We used the likelihood ratio test to evaluate whether X _rs z-score adds significantly to clinical predictors, including GA, birthweight (BW) and the National Institute of Child Health and Human Development (NICHD) BPD prediction model.

Results: 137 infants (median (interquartile range) 28.43 (26.11-30.29) weeks GA) were included; 44 (32%) developed BPD. X _rs z-score was significantly associated with the duration of respiratory support (R²=0.35). X _rs z-score was significantly higher in infants who developed BPD (p<0.001); the optimal cut-off value was 2.6, associated with 77% sensitivity and 80% specificity. In univariable analysis, per z-score increase in X _rs, the odds ratio for BPD increased by 60% and the respiratory support by 8 days. In multivariable analysis, X _rs z-score added significantly to the NICHD model and to GA and BW z-score to predict respiratory support duration (p=0.016 and p=0.014, respectively) and BPD development (p=0.003 and p<0.001, respectively).

Conclusion: X _rs z-score on the 7th day after birth improves the prediction of respiratory outcome in preterm infants.

Background: Few studies have investigated the influence of body mass index (BMI) trajectories on lung function covering the entire growth period.

Methods: We conducted a prospective study using data from the Swedish BAMSE birth cohort. Latent class mixture modelling was employed to examine the diversity in BMI z-scores from birth to 24 years of age. Participants with four or more BMI z-scores were included (n=3204, 78.4%). Pre-bronchodilator spirometry was tested at 8, 16 and 24 years, while post-bronchodilator spirometry, multiple-breath nitrogen washout (for lung clearance index) and urinary metabolomics data were assessed at 24 years.

Results: Six distinct BMI development groups were identified. Compared to the stable normal BMI group, the accelerated increasing BMI group exhibited reduced pre- and post-bronchodilator forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) ratio z-scores (pre: β= -0.26, 95% CI -0.44- -0.08; post: β= -0.22, 95% CI -0.39- -0.05), along with elevated lung clearance index (0.30, 95% CI 0.22-0.42) at 24 years. The persistent high BMI group demonstrated lower FEV₁ (-0.24, 95% CI -0.42- -0.05) and FVC (-0.27, 95% CI -0.45- -0.01) z-score growth between 16 and 24 years, and elevated lung clearance index (0.20, 95% CI 0.03-0.39) at 24 years. However, those impairments were not observed in the accelerated resolving BMI group. Conversely, the persistent low BMI group displayed persistently decreased FEV₁ and FVC from 8 to 24 years, as well as decreased lung function growth. Additionally, histidine-related metabolites were associated with pre- and post-bronchodilator FEV₁ (hypergeometric false discovery rate=0.008 and <0.001, respectively).

Conclusions: Early interventions aiming for normal BMI during childhood may contribute to improved lung health later in life.

Background: Tuberculosis (TB) remains a major cause of infectious disease mortality globally, with significant underdiagnosis perpetuating transmission. Tongue swab analysis has emerged as a promising non-invasive method for pulmonary TB diagnosis. This study evaluates the diagnostic accuracy of the TB-EASY quantitative PCR (qPCR) assay using tongue swab specimens.

Methods: In this prospective multicentre study, conducted across seven designated TB hospitals in China, 729 participants were included in the analysis. Tongue swabs were tested using the new TB-EASY assay from Hugobiotech, while sputum samples were analysed by Xpert MTB/RIF (Xpert), smear and culture tests. Diagnostic performance was compared to a composite microbiological reference standard (MRS).

Results: The TB-EASY assay demonstrated high diagnostic accuracy, with sensitivity and specificity of 89.6% and 96.2% compared to sputum Xpert, and 87.4% and 98.0% compared to the MRS. Sensitivity varied by bacterial load, ranging from 100% in high-load cases to 70.4% in very-low-load cases. The assay demonstrated robust performance in diverse epidemiological settings.

Conclusions: The TB-EASY qPCR assay using tongue swabs offers a reliable, non-invasive diagnostic alternative for pulmonary TB, especially where sputum collection is challenging. Its potential for wider use in high TB burden settings warrants further validation in community-based studies. Limitations include potential overestimation of sensitivity due to the selection of symptomatic patients and the use of sputum Xpert rather than Xpert Ultra. Additionally, the performance in non-sputum-producing patients remains untested, and the cost-effectiveness should be further evaluated to assess the feasibility of its implementation.